ABSTRACT BACKGROUND Concomitant syphilis and human immunodeficiency virus (HIV) infection is increasingly frequent in industrialized countries. METHODS From a large hospital cohort of HIV-infected patients followed up in the Paris area between 1998 and 2006, we examined the effect of early syphilis on plasma HIV-1 RNA levels and CD4 cell counts. We compared 282 HIV-1-infected men diagnosed as having incident primary or secondary syphilis with 1233 syphilis-free men matched for age (±5 years), sexual orientation, participating center, length of follow-up (±6 months), and immunologic and virologic status before the date of syphilis diagnosis (index date). Increase in viral load (VL) (plasma HIV-1 RNA) of at least 0.5 log or a rise to greater than 500 copies/mL in patients with previously controlled VL during the 6 months after the index date was analyzed, as were CD4 cell count variations and CD4 slope after the index date. RESULTS During the 6 months after the index date, VL increase was observed in 77 men with syphilis (27.3%) and in 205 syphilis-free men (16.6%) (adjusted odds ratio [aOR], 1.87; 95% CI, 1.40-2.49). Even in men with a VL of less than 500 copies/mL undergoing antiretroviral therapy, syphilis was associated with a higher risk of VL increase (aOR, 1.52; 95% CI, 1.02-2.26). The CD4 cell count decreased significantly (mean, -28/μL) compared with the syphilis-free group during the syphilis episode (P = .001) but returned to previous levels thereafter. CONCLUSIONS In HIV-infected men, syphilis was associated with a slight and transient decrease in the CD4 cell count and with an increase in VL, which implies that syphilis may increase the risk of HIV transmission, even in patients receiving antiretroviral therapy and with a VL of less than 500 copies/mL.

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Background Symptomatic early neurosyphilis with isolated acute multiple cranial nerves palsy as initial manifestation of HIV infection is very rare. It is caused by direct invasion of the central nervous system by the spirochete Treponema pallidum. Case Report A 31-year-old African-American homosexual man presented with bilateral hearing loss, constant vertigo, intermittent horizontal diplopia, and bilateral facial droop, which was associated with occipital headache without fever. Neurological examination revealed bilateral vestibulocochlear and facial nerve palsy. On brain magnetic resonance imaging (MRI) before and after administration of gadolinium, he was found to have extensive isolated basilar meningeal enhancement involving the midbrain, pons along the seven and eight nerves complex bilaterally, consistent with basal meningoencephalitis. Conclusions Neurosyphilis can present as initial manifestation of HIV infection with early involvement of basal meninges and cranial nerves. It is important to understand that neurosyphilis is still a significant disease with complex neurological presentation. Early diagnosis and treatment of neurosyphilis is crucial due to potential persistent disabilities that can be easily treated or even prevented.

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Incident syphilis infections continue to be especially prevalent among a core group of HIV-infected men who have sex with men (MSM). Because of synergy between syphilis and HIV infections, innovative means for controlling incident syphilis infections are needed.
Thirty MSM who had syphilis twice or more since their HIV diagnosis were randomized to receive either daily doxycycline prophylaxis or contingency management (CM) with incentive payments for remaining free of sexually transmitted diseases (STDs). Participants were tested for the bacterial STDs gonorrhea (Neisseria gonorrhoeae), chlamydia (Chlamydia trachomatis) and syphilis at weeks 12, 24, 36, and 48 and completed a behavioral risk questionnaire during each visit to assess number of partners, condom use, and drug use since the last visit. Generalized linear mixed models were used to analyze differences between arms in STD incidence and risk behaviors at follow-up.
Doxycycline arm participants were significantly less likely to test positive for any selected bacterial STD during 48 weeks of follow-up (odds ratio, 0.27; confidence interval, 0.09-0.83) compared with CM arm participants (P = 0.02).There were no significant self-reported risk behavior differences between the doxycycline and CM arms at follow-up.
Daily doxycycline taken prophylactically was associated with a decreased incidence of N. gonorrhoeae, C. trachomatis, or syphilis incident infections among a core group of HIV-infected MSM at high risk for these infections. Safe and effective biomedical tools should be included in the efforts to control transmission of syphilis, especially in this population. A randomized clinical trial should be conducted to confirm and extend these findings.

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BACKGROUND: Syphilis infection may potentiate transmission of HIV. We sought to determine the extent to which HIV acquisition was associated with syphilis infection within an HIV pre-exposure prophylaxis trial (iPrEx) and whether Emtricitabine/Tenofovir (FTC/TDF) modified that association. METHODS: The Pre-exposure Prophylaxis Initiative (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Syphilis prevalence at screening and incidence during follow-up were measured. Hazard ratios for the effect of incident syphilis on HIV acquisition were calculated. The effect of FTC/TDF on incident syphilis and HIV acquisition was assessed. RESULTS: Of 2499 individuals, there were 360 (14.4%) with positive RPR at screening; 333 (92.5%) had a positive confirmatory test, which did not differ between the arms (FTC/TDF vs placebo, p=0.81). The overall syphilis incidence during the trial was 7.3 cases per 100 person years. There was no difference in syphilis incidence between the study arms (FTC/TDF: 7.8 cases/per-year vs. placebo: 6.8, p=0.304). HIV incidence varied by incident syphilis (no syphilis: 2.8 vs incident syphilis: 8.0 cases per 100 person-years) reflecting a hazard ratio (HR) of 2.6, 95% confidence interval (CI) 1.6 to 4.4, p<0.001. There was no evidence for interaction between randomization to the FTC/TDF arm and incident syphilis on HIV incidence. CONCLUSIONS: In HIV-seronegative MSM, syphilis infection is associated with HIV acquisition in this pre-exposure prophylaxis (PrEP) trial; a syphilis diagnosis should prompt providers to offer PrEP unless otherwise contraindicated.

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